Characterization of a peptide adduct formed by N-acetoxy-2-amino-1-methyl- 6-phenylimidazo[4,5-b]pyridine (PhIP), a reactive intermediate of the food carcinogen PhIP

C. L. Chepanoske, K. Brown, Ken W Turteltaub, K. H. Dingley

Research output: Contribution to journalArticle

21 Citations (Scopus)

Abstract

2-Amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) is a member of a class of compounds known as the heterocyclic amines (HCAs) that are formed in meat during cooking. It is a multi-organ carcinogen in rodents forms adducts and with DNA and protein. Although protein adducts are not thought to be involved in cancer development, they may be useful as internal dosimeters of PhIP exposure and bioactivation. Towards the goals of characterizing the adducts formed in humans and the development of an assay for quantitation of adduct levels, we have characterized a peptide adduct formed by the putative genotoxic metabolite, N-acetoxy-PhIP. A model peptide with the internal sequence Leu-Gln-Lys-Cys-Pro-Tyr, which is homologous to a potential target sequence for HCAs in human serum albumin, was reacted with N-acetoxy-PhIP and an adduct was identified and further characterized by LC-ESI-MS/MS. N-acetoxy-PhIP is covalently bound to the peptide via cysteine and the exocyclic amino group of PhIP. Future work is needed to establish if this adduct is formed and is stable in vivo in humans following exposure to PhIP.

Original languageEnglish (US)
Pages (from-to)1367-1372
Number of pages6
JournalFood and Chemical Toxicology
Volume42
Issue number8
DOIs
StatePublished - Aug 2004
Externally publishedYes

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pyridines
carcinogens
Carcinogens
heterocyclic amines
peptides
Food
Peptides
Amines
cysteine
cooking
rodents
proteins
meat
DNA Adducts
Dosimeters
Meats
metabolites
Cooking
Human Development
Metabolites

Keywords

  • HCA, heterocyclic amine
  • IQ, 2-amino-3-methylimidazo[4,5-f] quinoline
  • LC-ESI-MS, liquid chromatography-electrospray ionization mass spectrometry
  • MS/MS, tandem mass spectrometry
  • PhIP, 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine

ASJC Scopus subject areas

  • Food Science
  • Toxicology

Cite this

Characterization of a peptide adduct formed by N-acetoxy-2-amino-1-methyl- 6-phenylimidazo[4,5-b]pyridine (PhIP), a reactive intermediate of the food carcinogen PhIP. / Chepanoske, C. L.; Brown, K.; Turteltaub, Ken W; Dingley, K. H.

In: Food and Chemical Toxicology, Vol. 42, No. 8, 08.2004, p. 1367-1372.

Research output: Contribution to journalArticle

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abstract = "2-Amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) is a member of a class of compounds known as the heterocyclic amines (HCAs) that are formed in meat during cooking. It is a multi-organ carcinogen in rodents forms adducts and with DNA and protein. Although protein adducts are not thought to be involved in cancer development, they may be useful as internal dosimeters of PhIP exposure and bioactivation. Towards the goals of characterizing the adducts formed in humans and the development of an assay for quantitation of adduct levels, we have characterized a peptide adduct formed by the putative genotoxic metabolite, N-acetoxy-PhIP. A model peptide with the internal sequence Leu-Gln-Lys-Cys-Pro-Tyr, which is homologous to a potential target sequence for HCAs in human serum albumin, was reacted with N-acetoxy-PhIP and an adduct was identified and further characterized by LC-ESI-MS/MS. N-acetoxy-PhIP is covalently bound to the peptide via cysteine and the exocyclic amino group of PhIP. Future work is needed to establish if this adduct is formed and is stable in vivo in humans following exposure to PhIP.",
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AB - 2-Amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) is a member of a class of compounds known as the heterocyclic amines (HCAs) that are formed in meat during cooking. It is a multi-organ carcinogen in rodents forms adducts and with DNA and protein. Although protein adducts are not thought to be involved in cancer development, they may be useful as internal dosimeters of PhIP exposure and bioactivation. Towards the goals of characterizing the adducts formed in humans and the development of an assay for quantitation of adduct levels, we have characterized a peptide adduct formed by the putative genotoxic metabolite, N-acetoxy-PhIP. A model peptide with the internal sequence Leu-Gln-Lys-Cys-Pro-Tyr, which is homologous to a potential target sequence for HCAs in human serum albumin, was reacted with N-acetoxy-PhIP and an adduct was identified and further characterized by LC-ESI-MS/MS. N-acetoxy-PhIP is covalently bound to the peptide via cysteine and the exocyclic amino group of PhIP. Future work is needed to establish if this adduct is formed and is stable in vivo in humans following exposure to PhIP.

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